Innovative Drug Release and Vaccine Delivery Systems

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: 10 June 2024 | Viewed by 23129

Special Issue Editors


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Guest Editor
Department of Pharmacology, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania
Interests: inflammation; anti-inflammatory drugs; depression; antidepressant drugs; biomarkers; drug delivery systems; in vivo animal models
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Guest Editor
Department of Pharmacology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
Interests: polymers; biocompatible; biodegradable; bioconjugates; nanoparticles; microparticles; drug delivery systems; biological targets; animal models
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to invite you to contribute to the Special Issue entitled “Innovative Drug Release and Vaccine Delivery Systems”, which aims to highlight recent advances in the field. Drug delivery research is a multidisciplinary effort ranging from basic science to clinical trials, aiming to develop advanced therapies for acute and chronic illnesses. Different approaches have been taken to improve drugs’ pharmacological profile, and to provide targeted and increased bioavailability. In addition, nanomaterials and nanotechnologies, as well as various biocompatible polymers, have gained attention in recent decades. We invite researchers to provide original research articles, as well as review articles, focusing on multiple issues about the design of original drug release and vaccine delivery systems, possibly revealing novel design technologies and biomaterials for drug delivery, including their obtainment, characterization, structure, original aspects, advantages, disadvantages, and various medical applications.

We look forward to receiving your contributions. 

Dr. Maria Bogdan
Prof. Dr. Liliana Mititelu-Tartau
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • biomaterials
  • biocompatible polymers
  • biocompatibility evaluation
  • drug delivery
  • vaccines
  • nanoparticles
  • structure–property relationship
  • bio-hybrid
  • in vitro and in vivo studies
  • medical applications of biomaterials

Published Papers (8 papers)

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Research

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20 pages, 3698 KiB  
Article
Co-Delivery of a Novel Lipidated TLR7/8 Agonist and Hemagglutinin-Based Influenza Antigen Using Silica Nanoparticles Promotes Enhanced Immune Responses
by Walid M. Abdelwahab, Sarah Auclair, Timothy Borgogna, Karthik Siram, Alexander Riffey, Hélène G. Bazin, Howard B. Cottam, Tomoko Hayashi, Jay T. Evans and David J. Burkhart
Pharmaceutics 2024, 16(1), 107; https://doi.org/10.3390/pharmaceutics16010107 - 13 Jan 2024
Cited by 1 | Viewed by 1699
Abstract
Co-delivery of antigens and adjuvants to the same antigen-presenting cells (APCs) can significantly improve the efficacy and safety profiles of vaccines. Here, we report amine-grafted silica nanoparticles (A-SNP) as a tunable vaccine co-delivery platform for TLR7/8 agonists along with the recombinant influenza antigen [...] Read more.
Co-delivery of antigens and adjuvants to the same antigen-presenting cells (APCs) can significantly improve the efficacy and safety profiles of vaccines. Here, we report amine-grafted silica nanoparticles (A-SNP) as a tunable vaccine co-delivery platform for TLR7/8 agonists along with the recombinant influenza antigen hemagglutinin H7 (H7) to APCs. A-SNP of two different sizes (50 and 200 nm) were prepared and coated with INI-4001 at different coating densities, followed by co-adsorption of H7. Both INI-4001 and H7 showed >90% adsorption to the tested A-SNP formulations. TNF-α and IFN-α cytokine release by human peripheral blood mononuclear cells as well as TNF-α, IL-6, and IL-12 release by mouse bone marrow-derived dendritic cells revealed that the potency of the INI-4001-adsorbed A-SNP (INI-4001/A-SNP) formulations was improved relative to aqueous formulation control. This improved potency was dependent on particle size and ligand coating density. In addition, slow-release profiles of INI-4001 were measured from INI-4001/A-SNP formulations in plasma with 30–50% INI-4001 released after 7 days. In vivo murine immunization studies demonstrated significantly improved H7-specific humoral and Th1/Th17-polarized T cell immune responses with no observed adverse reactions. Low-density 50 nm INI-4001/A-SNP elicited significantly higher IFN-γ and IL-17 induction over that of the H7 antigen-only group and INI-4001 aqueous formulation controls. In summary, this work introduces an effective and biocompatible SNP-based co-delivery platform that enhances the immunogenicity of TLR7/8 agonist-adjuvanted subunit influenza vaccines. Full article
(This article belongs to the Special Issue Innovative Drug Release and Vaccine Delivery Systems)
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22 pages, 2785 KiB  
Article
Nanostructured Lipid Carriers Enriched Hydrogels for Skin Topical Administration of Quercetin and Omega-3 Fatty Acid
by Marlene Lúcio, Nicole Giannino, Sérgio Barreira, José Catita, Hugo Gonçalves, Artur Ribeiro, Eduarda Fernandes, Isabel Carvalho, Hugo Pinho, Fátima Cerqueira, Marco Biondi and Carla M. Lopes
Pharmaceutics 2023, 15(8), 2078; https://doi.org/10.3390/pharmaceutics15082078 - 3 Aug 2023
Cited by 5 | Viewed by 1739
Abstract
Chronic skin exposure to external hostile agents (e.g., UV radiation, microorganisms, and oxidizing chemicals) may increase oxidative stress, causing skin damage and aging. Because of their well-known skincare and protective benefits, quercetin (Q) and omega-3 fatty acids (ω3) have attracted the [...] Read more.
Chronic skin exposure to external hostile agents (e.g., UV radiation, microorganisms, and oxidizing chemicals) may increase oxidative stress, causing skin damage and aging. Because of their well-known skincare and protective benefits, quercetin (Q) and omega-3 fatty acids (ω3) have attracted the attention of the dermocosmetic and pharmaceutical sectors. However, both bioactives have inherent properties that limit their efficient skin delivery. Therefore, nanostructured lipid carriers (NLCs) and enriched PFC® hydrogels (HGs) have been developed as a dual-approach vehicle for Q and/or ω3 skin topical administration to improve bioactives’ stability and skin permeation. Two NLC formulations were prepared with the same lipid composition but differing in surfactant composition (NLC1—soy lecithin and poloxamer 407; NLC2—Tween® 80 and dioctyl sodium sulfosuccinate (DOSS)), which have an impact on physicochemical properties and pharmaceutical and therapeutic performance. Despite both NLCs presenting high Q loading capacity, NLC2′s physicochemical properties make them more suitable for topical skin administration and ensure longer colloidal stability. Additionally, NLC2 demonstrated a more sustained Q release, indicating higher bioactive storage while improving permeability. The occlusive effect of NLCs-enriched HGs also has a positive impact on skin permeability. Q-loaded NLC2, with or without ω3, -enriched HGs demonstrated efficacy as antioxidant and photoprotective formulations as well as effective reduction in S. aureus growth, indicating that they constitute a promising approach for topical skin administration to prevent skin aging and other damaging cutaneous processes. Full article
(This article belongs to the Special Issue Innovative Drug Release and Vaccine Delivery Systems)
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22 pages, 6102 KiB  
Article
Modified Linear Peptides Effectively Silence STAT-3 in Breast Cancer and Ovarian Cancer Cell Lines
by Dindyal Mandal, Sandeep Lohan, Muhammad Imran Sajid, Abdulelah Alhazza, Rakesh Kumar Tiwari, Keykavous Parang and Hamidreza Montazeri Aliabadi
Pharmaceutics 2023, 15(2), 666; https://doi.org/10.3390/pharmaceutics15020666 - 16 Feb 2023
Cited by 1 | Viewed by 2183
Abstract
RNA interference (RNAi) has drawn enormous attention as a powerful tool because of its capability to interfere with mRNA and protein production. However, designing a safe and efficient delivery system in RNAi therapeutics remains challenging. Herein, we have designed and synthesized several linear [...] Read more.
RNA interference (RNAi) has drawn enormous attention as a powerful tool because of its capability to interfere with mRNA and protein production. However, designing a safe and efficient delivery system in RNAi therapeutics remains challenging. Herein, we have designed and synthesized several linear peptides containing tryptophan (W) and arginine (R) residues separated by the β-alanine (βA) spacer and attached to a lipophilic fatty acyl chain, cholesterol, or PEG. The peptide backbone sequences were: Ac-C-βA-βA-W4-βA-βA-R4-CO-NH2 and Ac-K-βA-βA-W4-βA-βA-R4-CO-NH2, with only a difference in N-terminal amino acid. The cysteine side chain in the first sequence was used for the conjugation with PEG2000 and PEG550. Alternatively, the side chain of lysine in the second sequence was used for conjugation with cholesterol or oleic acid. We hypothesized that amphiphilic peptides and optimum fatty acyl chain or PEG could function as an effective siRNA carrier by complementing each structural component’s self-assembly and membrane internalization properties. None of the designed peptides showed cytotoxicity up to 10 µM. Serum stability studies suggested that the newly designed peptides efficiently protected siRNA against early degradation by nucleases. Flow cytometry analysis indicated 50–90% cellular uptake of siRNA using the newly developed modified linear peptides (MLPs). Western blot results revealed more than 90% protein downregulation after targeting STAT3 in MDA-MB-231 and SKOV-3 cell lines. In summary, a new peptide class was developed to safely and efficiently deliver siRNA. Full article
(This article belongs to the Special Issue Innovative Drug Release and Vaccine Delivery Systems)
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Review

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18 pages, 3262 KiB  
Review
Immune Specific and Tumor-Dependent mRNA Vaccines for Cancer Immunotherapy: Reprogramming Clinical Translation into Tumor Editing Therapy
by Theodora Katopodi, Savvas Petanidis, Eirini Grigoriadou, Doxakis Anestakis, Charalampos Charalampidis, Ioanna Chatziprodromidou, George Floros, Panagiotis Eskitzis, Paul Zarogoulidis, Charilaos Koulouris, Christina Sevva, Konstantinos Papadopoulos, Panagiota Roulia, Stylianos Mantalovas, Marios Dagher, Alexandros Vasileios Karakousis, Nikolaos Varsamis, Konstantinos Vlassopoulos, Vasiliki Theodorou, Chrysi Maria Mystakidou, Nikolaos Iason Katsios, Konstantinos Farmakis and Christoforos Kosmidisadd Show full author list remove Hide full author list
Pharmaceutics 2024, 16(4), 455; https://doi.org/10.3390/pharmaceutics16040455 - 25 Mar 2024
Viewed by 1336
Abstract
Extensive research into mRNA vaccines for cancer therapy in preclinical and clinical trials has prepared the ground for the quick development of immune-specific mRNA vaccines during the COVID-19 pandemic. Therapeutic cancer vaccines based on mRNA are well tolerated, and are an attractive choice [...] Read more.
Extensive research into mRNA vaccines for cancer therapy in preclinical and clinical trials has prepared the ground for the quick development of immune-specific mRNA vaccines during the COVID-19 pandemic. Therapeutic cancer vaccines based on mRNA are well tolerated, and are an attractive choice for future cancer immunotherapy. Ideal personalized tumor-dependent mRNA vaccines could stimulate both humoral and cellular immunity by overcoming cancer-induced immune suppression and tumor relapse. The stability, structure, and distribution strategies of mRNA-based vaccines have been improved by technological innovations, and patients with diverse tumor types are now being enrolled in numerous clinical trials investigating mRNA vaccine therapy. Despite the fact that therapeutic mRNA-based cancer vaccines have not yet received clinical approval, early clinical trials with mRNA vaccines as monotherapy and in conjunction with checkpoint inhibitors have shown promising results. In this review, we analyze the most recent clinical developments in mRNA-based cancer vaccines and discuss the optimal platforms for the creation of mRNA vaccines. We also discuss the development of the cancer vaccines’ clinical research, paying particular attention to their clinical use and therapeutic efficacy, which could facilitate the design of mRNA-based vaccines in the near future. Full article
(This article belongs to the Special Issue Innovative Drug Release and Vaccine Delivery Systems)
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35 pages, 10219 KiB  
Review
Chemistry and Art of Developing Lipid Nanoparticles for Biologics Delivery: Focus on Development and Scale-Up
by Rijo John, Jasmin Monpara, Shankar Swaminathan and Rahul Kalhapure
Pharmaceutics 2024, 16(1), 131; https://doi.org/10.3390/pharmaceutics16010131 - 19 Jan 2024
Cited by 2 | Viewed by 3111
Abstract
Lipid nanoparticles (LNPs) have gained prominence as primary carriers for delivering a diverse array of therapeutic agents. Biological products have achieved a solid presence in clinical settings, and the anticipation of creating novel variants is increasing. These products predominantly encompass therapeutic proteins, nucleic [...] Read more.
Lipid nanoparticles (LNPs) have gained prominence as primary carriers for delivering a diverse array of therapeutic agents. Biological products have achieved a solid presence in clinical settings, and the anticipation of creating novel variants is increasing. These products predominantly encompass therapeutic proteins, nucleic acids and messenger RNA. The advancement of efficient LNP-based delivery systems for biologics that can overcome their limitations remains a highly favorable formulation strategy. Moreover, given their small size, biocompatibility, and biodegradation, LNPs can proficiently transport therapeutic moiety into the cells without significant toxicity and adverse reactions. This is especially crucial for the existing and upcoming biopharmaceuticals since large molecules as a group present several challenges that can be overcome by LNPs. This review describes the LNP technology for the delivery of biologics and summarizes the developments in the chemistry, manufacturing, and characterization of lipids used in the development of LNPs for biologics. Finally, we present a perspective on the potential opportunities and the current challenges pertaining to LNP technology. Full article
(This article belongs to the Special Issue Innovative Drug Release and Vaccine Delivery Systems)
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34 pages, 9560 KiB  
Review
Ginkgo Biloba and Long COVID: In Vivo and In Vitro Models for the Evaluation of Nanotherapeutic Efficacy
by Thelma Akanchise and Angelina Angelova
Pharmaceutics 2023, 15(5), 1562; https://doi.org/10.3390/pharmaceutics15051562 - 22 May 2023
Cited by 10 | Viewed by 3417
Abstract
Coronavirus infections are neuroinvasive and can provoke injury to the central nervous system (CNS) and long-term illness consequences. They may be associated with inflammatory processes due to cellular oxidative stress and an imbalanced antioxidant system. The ability of phytochemicals with antioxidant and anti-inflammatory [...] Read more.
Coronavirus infections are neuroinvasive and can provoke injury to the central nervous system (CNS) and long-term illness consequences. They may be associated with inflammatory processes due to cellular oxidative stress and an imbalanced antioxidant system. The ability of phytochemicals with antioxidant and anti-inflammatory activities, such as Ginkgo biloba, to alleviate neurological complications and brain tissue damage has attracted strong ongoing interest in the neurotherapeutic management of long COVID. Ginkgo biloba leaf extract (EGb) contains several bioactive ingredients, e.g., bilobalide, quercetin, ginkgolides A–C, kaempferol, isorhamnetin, and luteolin. They have various pharmacological and medicinal effects, including memory and cognitive improvement. Ginkgo biloba, through its anti-apoptotic, antioxidant, and anti-inflammatory activities, impacts cognitive function and other illness conditions like those in long COVID. While preclinical research on the antioxidant therapies for neuroprotection has shown promising results, clinical translation remains slow due to several challenges (e.g., low drug bioavailability, limited half-life, instability, restricted delivery to target tissues, and poor antioxidant capacity). This review emphasizes the advantages of nanotherapies using nanoparticle drug delivery approaches to overcome these challenges. Various experimental techniques shed light on the molecular mechanisms underlying the oxidative stress response in the nervous system and help comprehend the pathophysiology of the neurological sequelae of SARS-CoV-2 infection. To develop novel therapeutic agents and drug delivery systems, several methods for mimicking oxidative stress conditions have been used (e.g., lipid peroxidation products, mitochondrial respiratory chain inhibitors, and models of ischemic brain damage). We hypothesize the beneficial effects of EGb in the neurotherapeutic management of long-term COVID-19 symptoms, evaluated using either in vitro cellular or in vivo animal models of oxidative stress. Full article
(This article belongs to the Special Issue Innovative Drug Release and Vaccine Delivery Systems)
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20 pages, 2717 KiB  
Review
Layer-by-Layer Nanoassemblies for Vaccination Purposes
by Eduardo Guzmán, Francisco Ortega and Ramón G. Rubio
Pharmaceutics 2023, 15(5), 1449; https://doi.org/10.3390/pharmaceutics15051449 - 10 May 2023
Cited by 2 | Viewed by 1886
Abstract
In recent years, the availability of effective vaccines has become a public health challenge due to the proliferation of different pandemic outbreaks which are a risk for the world population health. Therefore, the manufacturing of new formulations providing a robust immune response against [...] Read more.
In recent years, the availability of effective vaccines has become a public health challenge due to the proliferation of different pandemic outbreaks which are a risk for the world population health. Therefore, the manufacturing of new formulations providing a robust immune response against specific diseases is of paramount importance. This can be partially faced by introducing vaccination systems based on nanostructured materials, and in particular, nanoassemblies obtained by the Layer-by-Layer (LbL) method. This has emerged, in recent years, as a very promising alternative for the design and optimization of effective vaccination platforms. In particular, the versatility and modularity of the LbL method provide very powerful tools for fabricating functional materials, opening new avenues on the design of different biomedical tools, including very specific vaccination platforms. Moreover, the possibility to control the shape, size, and chemical composition of the supramolecular nanoassemblies obtained by the LbL method offers new opportunities for manufacturing materials which can be administered following specific routes and present very specific targeting. Thus, it will be possible to increase the patient convenience and the efficacy of the vaccination programs. This review presents a general overview on the state of the art of the fabrication of vaccination platforms based on LbL materials, trying to highlight some important advantages offered by these systems. Full article
(This article belongs to the Special Issue Innovative Drug Release and Vaccine Delivery Systems)
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43 pages, 14644 KiB  
Review
Cocrystals by Design: A Rational Coformer Selection Approach for Tackling the API Problems
by Maan Singh, Harsh Barua, Vaskuri G. S. Sainaga Jyothi, Madhukiran R. Dhondale, Amritha G. Nambiar, Ashish K. Agrawal, Pradeep Kumar, Nalini R. Shastri and Dinesh Kumar
Pharmaceutics 2023, 15(4), 1161; https://doi.org/10.3390/pharmaceutics15041161 - 6 Apr 2023
Cited by 8 | Viewed by 6706
Abstract
Active pharmaceutical ingredients (API) with unfavorable physicochemical properties and stability present a significant challenge during their processing into final dosage forms. Cocrystallization of such APIs with suitable coformers is an efficient approach to mitigate the solubility and stability concerns. A considerable number of [...] Read more.
Active pharmaceutical ingredients (API) with unfavorable physicochemical properties and stability present a significant challenge during their processing into final dosage forms. Cocrystallization of such APIs with suitable coformers is an efficient approach to mitigate the solubility and stability concerns. A considerable number of cocrystal-based products are currently being marketed and show an upward trend. However, to improve the API properties by cocrystallization, coformer selection plays a paramount role. Selection of suitable coformers not only improves the drug’s physicochemical properties but also improves the therapeutic effectiveness and reduces side effects. Numerous coformers have been used till date to prepare pharmaceutically acceptable cocrystals. The carboxylic acid-based coformers, such as fumaric acid, oxalic acid, succinic acid, and citric acid, are the most commonly used coformers in the currently marketed cocrystal-based products. Carboxylic acid-based coformers are capable of forming the hydrogen bond and contain smaller carbon chain with the APIs. This review summarizes the role of coformers in improving the physicochemical and pharmaceutical properties of APIs, and deeply explains the utility of afore-mentioned coformers in API cocrystal formation. The review concludes with a brief discussion on the patentability and regulatory issues related to pharmaceutical cocrystals. Full article
(This article belongs to the Special Issue Innovative Drug Release and Vaccine Delivery Systems)
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